Adhesion and costimulation of proliferative responses of human γδ T cells by interaction of VLA-4 and VLA-5 with fibronectin

Mark V Avdalovic, Dana Fong, Bent Formby

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The very late antigens, VLA-4 and VLA-5 belong to the β1 subfamily of integrins and have been identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3 and VLA-6 expressed on human CD3+ CD4- CD8- γδTCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL-2 receptor) but not resting CD25low γδT cells specifically adhere to FN. The binding capacity is inhibited by the synthetic peptide GRGDSP which inhibits adhesion mediated by VLA-5 and a functional mAb directed against the α4 subunit. Most FN binding is mediated by VLA-4. Additionally, resting γδ T cells cultured on coimmobilized anti-TCRδ1 mAb and FN or the 40 kDa fragment (which contains the adhesion site in the IIICS domain recognized by VLA-4) for 96 h in the absence of exogeneous IL-2 showed significant increase in proliferation when compared to that of resting γδ T cells cultured on immobilized anti-TCRδ1 mAb alone. Also expression of CD25 was significantly enhanced on cells cultured on coimmobilized anti-TCRδ1 mAb and FN, indicative of T cell activation. Cross-linking of VLA-4 and VLA-5 molecules costimulated expansion of resting γδ T cells induced by cross-linked TCRδ1. These results suggest that the γδ T cell β1 integrins, VLA-4 and VLA-5, may function in a dual capacity as signalling and adhesion molecules.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalImmunology Letters
Volume35
Issue number2
DOIs
StatePublished - 1993
Externally publishedYes

Fingerprint

Integrin alpha5beta1
Integrin alpha4beta1
Fibronectins
Cell Communication
T-Lymphocytes
Integrins
glycyl-arginyl-glycyl-aspartyl-seryl-proline
Integrin alpha3beta1
Integrin alpha6beta1
Interleukin-2 Receptors
Interleukin-2
Cultured Cells
Flow Cytometry
Peptides

Keywords

  • Costimulation
  • Human γδ TCR
  • β1 Integrins

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Adhesion and costimulation of proliferative responses of human γδ T cells by interaction of VLA-4 and VLA-5 with fibronectin. / Avdalovic, Mark V; Fong, Dana; Formby, Bent.

In: Immunology Letters, Vol. 35, No. 2, 1993, p. 101-108.

Research output: Contribution to journalArticle

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